Uridine

EnginZyme and Ajinomoto Bio-Pharma Services have developed a patented process to manufacture pseudouridine at industrial scale using biocatalysis in a sustainable, low-waste, patented process carried out in a cGMP* facility EnginZyme is in talks to help alleviate supply chain difficulties in low- and middle-income countries 2023 Nobel laureates discovered how pseudouridine could make mRNA suitable for vaccines STOCKHOLM--(BUSINESS WIRE)-- EnginZyme AB, a deep-tech company whose cell-free biomanufacturing technology uses the power of enzymes to create sustainable products and processes for a variety of industries, announced that it had patented a process to synthesize pseudouridine, a key ingredient in mRNA COVID-19 vaccines. EnginZyme and its CDMO partner, Ajinomoto Bio-Pharma Services, specialized in scale up and cGMP* manufacturing of small molecules and other high-value fine chemicals, said they could provide pseudouridine at a discount to buyers taking part in efforts to bolster the global supply chain of vaccine ingredients. The companies said they had already synthesized enough pseudouridine for more than half a billion doses of vaccine in a facility that is fully cGMP* compliant. The enzymatic process EnginZyme has perfected is cleaner and more efficient than the chemical synthesis methods currently used. A critical impurity, alpha-pseudouridine, which is a by-product of the chemical synthesis of beta-pseudouridine, is eliminated in EnginZyme's patented enzymatic synthesis. For more technical information, see our website. The 2023 Nobel Prize for Physiology or Medicine was awarded to Katalin Karikó and Drew Weissman, the pair who discovered that changing a chemical building block of messenger RNA – substituting pseudouridine for uridine – eliminated an inflammatory side effect that stalled development of vaccines based on mRNA. They made this discovery more than 15 years before the COVID-19 pandemic. During the COVID-19 crisis, the World Health Organization found that low- and middle-income countries were suffering from a lack of vaccine doses amid production and supply constraints, hoarding by wealthy countries, and prioritization of sales to governments that could pay the highest prices. "Not long after we discovered the process for making pseudouridine, we realized that we could produce a pure version at scale for much less than it was going for on the market," said Karim Engelmark Cassimjee, CEO of EnginZyme. "We decided the right thing to do would be to use this discovery to help make the global healthcare supply chain more resilient." He added that academic and nonprofit organizations could apply to receive free samples for research purposes. Geert Schelkens, R&D Manager at Ajinomoto Bio-Pharma Services, said: "The scale-up of a biocatalytic process and a green workup results in a drastic reduction of the compound's footprint. This achievement nicely aligns with our sustainability ambitions. This project with EnginZyme has been particularly rewarding because of its potential to improve the global supply chain for vaccine ingredients.” N1-methylpseudouridine-5’-triphosphate, which is derived from pseudouridine, helps stabilize and reduce the immunogenicity of mRNA. Messenger RNA technology made headlines through the successful COVID-19 vaccines produced by Pfizer-BioNTech and Moderna, and since then, an increasing number of early-stage therapeutics and emerging vaccines have been based on the technology. "Synthesizing pseudouridine with enzymes is so much more efficient than the chemical synthesis that is common today," said Matthew Thompson, head of enzyme development and innovation at EnginZyme. "It's a perfect example of what we are striving for: zero waste, less energy, and a cleaner result. We want to apply this across the spectrum of chemical manufacturing." *Current Good Manufacturing Practice regulations, enforced by the U.S. FDA, provide for systems that assure proper design, monitoring, and control of manufacturing processes and facilities. About EnginZyme EnginZyme is changing chemistry for good. We are enabling the shift to biomanufacturing by unlocking the power of enzymes for more cost-efficient and sustainable production of everyday products. Our patented enzyme immobilisation technology enables biomanufacturing without living organisms. It can be deployed using the same tools and techniques used in traditional chemical manufacturing, with lower costs and a much smaller environmental footprint. Based in Stockholm, EnginZyme is a growing company with a multidisciplinary team of experts in biocatalysis, organic chemistry, enzyme and process engineering, as well as AI and machine learning. This elite team is uniquely positioned to develop complete processes from techno-economic analysis all the way to industrial manufacture, incorporating a high degree of automation for safe, rapid, and reliable development. EnginZyme has been recognised as a Technology pioneer by the World Economic Forum and was selected to the Global Cleantech 100 list in 2022 and 2023. About Ajinomoto Bio-Pharma Services Ajinomoto Bio-Pharma Services is a fully integrated contract development and manufacturing organization with sites in Belgium, United States, Japan, and India, providing comprehensive development, cGMP manufacturing, and aseptic fill finish services for small and large molecule APIs and intermediates. Ajinomoto Bio-Pharma Services offers a broad range of innovative platforms and capabilities for pre-clinical and pilot programs to commercial quantities, including high potency APIs (HPAPI), biocatalysis, continuous flow manufacturing, Corynex® protein expression technology, oligonucleotide synthesis, antibody drug conjugations (ADC), and more. Ajinomoto Bio-Pharma Services is dedicated to providing a high level of quality and service to meet our client’s needs. Learn more: View source version on businesswire.com: Contacts Business development Karl Johan Tärbe karljohan@enginzyme.com Media Bogert-Magnier Communications James Connell jim@bogert-magnier.com +33 6 2152 1955 Elodie Doan Van elodie@bogert-magnier.com +33 6 8099 8881 Source: EnginZyme AB View this news release online at:

2023年诺贝尔生理学或医学奖揭晓。 2023年诺贝尔生理学或医学奖揭晓。 获得者为卡塔琳·卡里科（Katalin Karikó）和德鲁·魏斯曼（Drew Weissman），获奖理由为“表彰他们在核苷碱基修饰方面的发现，这些发现使得针对COVID-19的有效mRNA疫苗得以开发出来”。 接下来，咱们就一起来回顾mRNA疫苗整整60年的研发史。 上个世纪40年代至60年代，是生命科学的黄金时代。 1944年，细菌学家埃弗里（Oswald Theodore Avery）用肺炎双球菌转化实验证明了DNA才是遗传物质，但是DNA与蛋白质之间究竟是如何联系起来的，科学家仍莫衷一是。 1947年，生物化学家André Boivin发挥自己的想象力，提出DNA是经过RNA完成蛋白质的合成。 1961年，Sydney Brenner、François Jacob和Jim Watson等共9人，在《自然》杂志发表两篇背靠背的论文，宣布分离到了mRNA。首次证实了mRNA的存在及功能。 1965年，英国科学家A.D.Bangham，M.M.Standish和J.C.Watkins制造出首个脂质体。 1969年，Raymond E.Lockard和Jerry B.Lingrel用分离的mRNA在体外合成蛋白质。 1978年，英国国家医学研究所Giorgos J. Dimitriadis团队和伊利诺伊大学芝加哥分校Sheldon Dray团队，同时首次成功将脂质体包裹的mRNA递送至细胞内部。 1984年，哈佛大学的P.A. Krieg和D.A. Melton首次在实验室合成mRNA。 1989年，索尔克生物研究所的R W Malone，P L Felgner和I M Verma用阳离子脂质体将mRNA递送到人类细胞。 1993年，法国国家健康与医学研究院的Frédéric Martinon等在小鼠体内测试首个预防流感的脂质体mRNA疫苗。 1995年，脂质体包裹的药物首次获得FDA的批准。 2005年，宾夕法尼亚大学医学院的卡塔琳·卡里科（Katalin Karikó）和德鲁·魏斯曼（Drew Weissman），首次发现用假尿苷（pseudouridine）替换mRNA里的尿苷（uridine），能够让合成的mRNA免受免疫系统的攻击，而且显著增强了mRNA表达蛋白的能力。 2013年，首个预防传染病（狂犬病）的mRNA疫苗开展临床试验。 2020年，mRNA新冠疫苗开展临床试验，且获得紧急使用授权（EUA）。